Vivo experiments using mice with cardiomyocyte-specific deletion of Tgfbr1(encoding TGF-β receptor 1, ALK5) or Tgfbr2(encoding TGF-β receptor 2) in non-reperfused MI models revealed that TGF-β signaling promotes left ventricular rupture by suppressing the transcription of genes encoding cardioprotective proteins such as IL-33(Interleukin-33), growth differentiation factor 15, and thrombospondin-4 (TSP4) (56). This evidence concerns the gene THBS4 and myocardial infarction.